This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cigarette smoking is among the most serious and costly health problems in the world today. While a number of treatments are currently available, real world long-term success rates for quitting remain disappointingly low. We propose to pilot test a novel treatment for smoking cessation that translates findings from basic learning neuroscience to an applied clinical protocol. Specifically, we will combine a promising behavioral therapy with a pharmacological manipulation expected to accelerate therapeutic response rates and test it against a control condition. The purpose of this study is to determine if frequent cigarette smokers (e.g. 10 cigarettes a day) are more likely to quit smoking when given D-Cycloserine during four extinction sessions in which they will smoke denicotinized (DN) cigarettes aimed at dissociating the act of smoking from the pleasurable pharmacological effects of nicotine. We hypothesize that subjects will reach quitting milestones quicker and in greater numbers than will the controls.